4.7 Article

Automated pattern-guided principal component analysis vs expert-based immunophenotypic classification of B-cell chronic lymphoproliferative disorders: a step forward in the standardization of clinical immunophenotyping

Journal

LEUKEMIA
Volume 24, Issue 11, Pages 1927-1933

Publisher

NATURE PUBLISHING GROUP
DOI: 10.1038/leu.2010.160

Keywords

haematological malignancies; flow cytometry; immunophenotyping; FCS data; principal component analysis; B-cell chronic lymphoproliferative disorders

Funding

  1. Spanish Network of Cancer Research Centers [ISCIII RTICC-RD06/0020/0035-FEDER]
  2. Fondo de Investigacion Sanitaria [FIS 08/90881]
  3. Ministerio de Ciencia e Innovacion (Madrid, Spain)
  4. Ministerio de Educacion y Ciencia, (Madrid, Spain) [PHB 2004-0800-PC]
  5. Consejeria de Educacion [SA016-A-09]
  6. Junta de Castilla y Leon, Valladolid, Spain
  7. CAPES/Ministerio da Educacao (Brasilia, Brazil)
  8. EuroFlow Consortium [LSHB-CT-2006-018708]
  9. European Commission
  10. Cancer Research Foundation
  11. University of Salamanca (Salamanca, Spain)
  12. CNPq- Brazilian National Research Council, Brasilia, Brazil [305306/2004-9, 558147/2008-9, 478234/2007-4]
  13. FAPERJ-Fundacao de amparo a pesquisa do Rio de Janeiro, (Rio de Janeiro, Brazil) [26/110.301/2007, E-26/102-781/2008]
  14. Jovens Pesquisadores [03/2006]
  15. Fundacion Carolina, Spain
  16. Fundacion Marcelino Botin (Madrid, Spain)

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Immunophenotypic characterization of B-cell chronic lymphoproliferative disorders (B-CLPD) is becoming increasingly complex due to usage of progressively larger panels of reagents and a high number of World Health Organization (WHO) entities. Typically, data analysis is performed separately for each stained aliquot of a sample; subsequently, an expert interprets the overall immunophenotypic profile (IP) of neoplastic B-cells and assigns it to specific diagnostic categories. We constructed a principal component analysis (PCA)-based tool to guide immunophenotypic classification of B-CLPD. Three reference groups of immunophenotypic data files-FB-cell chronic lymphocytic leukemias (B-CLL; n = 10), mantle cell (MCL; n = 10) and follicular lymphomas (FL; n = 10)-were built. Subsequently, each of the 175 cases studied was evaluated and assigned to either one of the three reference groups or to none of them (other B-CLPD). Most cases (89%) were correctly assigned to their corresponding WHO diagnostic group with overall positive and negative predictive values of 89 and 96%, respectively. The efficiency of the PCA-based approach was particularly high among typical B-CLL, MCL and FL vs other B-CLPD cases. In summary, PCA-guided immunophenotypic classification of B-CLPD is a promising tool for standardized interpretation of tumor IP, their classification into well-defined entities and comprehensive evaluation of antibody panels. Leukemia (2010) 24, 1927-1933; doi:10.1038/leu.2010.160; published online 16 September 2010

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